Catalytic amidization process



Patented Jan. 25, 1949 S TAT i' S arsnr 'FFE CATALYTIC AMIDIZETION PR'OGESS I Paul W. Garbo,,Freeport,.- NrYa N Drawing. Application November 14, 1946,

Serial No. 7093M Claims.

This application is a division of the copending application, Serial No. 470, fi d Dec ber 3.1; v1942, now Patent No. 2,419,831, issued 'April 29, 194-37.

This invention relates to the amidization of pyridine monocarboxylic acids and, more parvolves the formation of ammonium nicotinate,

which-may be obtained by merely neutralizing nicotinic acid with ammonium hydroxide, and splitting off With-the aid of heat a molecule of water from each molecule of ammonium nicotinate to leave amolecule of nicotinamide.

However, in the latter step, since ammonium,

nicotinate is not a verystable compound, heat tends to decompose thenicotinate into the original nicotinic acid and ammonia. Accordingly, thismethod has led to poor yields of nicotinamide and cumbersome separation and recycling techniques for unconverted material.

Considerable improvement in this process was efiectedwhen ammonia gas was bubbled up through the mass of molten ammonium nicotina't'e undergoing the'heat treatment Thus, by bubbling ammonia through molten ammonium nicotinate at an elevated temperature, e. g; about 160-170 C. conversions as high as about 85% were effected. That is to say, the final reaction mass would show by analysis to comprise about 85% nicotinamide andabout 15% nicotinic acid as such or as its salt. Even to reach 85% conversion, howeventhetime of heating and bubbling ammonia ran intomany hours; higher conversions were possible but the time of reaction became unreasonably long for usual commercial practice.

Furthermore, from such a reaction mass, the

recovery of nicot namidein a form meeting'present stringent specifications for melting point, color, pI-I, ash, etc., has required cumbersome, t me-consuming and expensive procedures- Also,

in View of the higlfroost of nicotinic acid;it"has been necessary to recover, with some difi'lculty and expense, the unconverted acid for reuse in a subsequent, reaction.

invention therefore has as principal object, the provision of a method for the amidization of py'ridinez-monocarboxylic acids which is characterized by its simplicity, the speed of reaction and excellent yield.

A further object is. to produce the amides of pyridine monocarboxyl'ic' acids without recourse to the. use of ammoniagas with its attendant difficulties anddisadvantages; in place of ammonia, llrea'is employedasithe amidizing agent.

Another object" ofxmy invention is to facilitate the recovery of the amides in highpurity from their reaction masses.

A, still. furtheriobject is to avoid: the usual neutrali'zation. step: vfor .convert'ing pyridine monocarboxylic acidsto the. ammonium salts,'which step is wasteful: in the consumption of energy and timewhi'chsare-required to remove the water of? the neutralization reaction.

Other objectsof my invention will become apparentt'rom' the disclosure which follows.

The-inventionis based on the discovery that pyridine=monocarboxylic acids are converted to the correspondingamides simply by reacting the acids with molten urea in the presence of a catalyst of the 'amidization reaction.

According to the invention, the desired pyridine monocarboxyl ic acid is made to react with the" molten urea in any convenient manner such as mixing the comminuted acid and urea and heating the mixture until it becomes fluid or introducing the acid-gradually into a molten mass of urea... While thereaction starts at about the meltinglpoint'ofurea, viz., (3., highertemperatures are usually employed to promote the reaction. The reaction mass is maintained in the heated fluid: state until periodic analyses of the reaction-massindicate that the reaction has come to" a satisfactory stage of. completion. Thereupon the produced amide may be separated from the reaction mass comprising, besides the amide, unreacted. material, and derivativesand degradation products of urea, e. g., biuret and cyanuric acid, by any of the known methods.

It. appears that in the course of the reaction an appreciable proportion of the urea used is converted to biuret and cyanuric acid. Consequently, while one-halfmolof urea with its two NI-I'z' 'grounsshould theoreticall sufi'ice to convert one mol of pyridine monooarboxylic acid to the amide; as a practical matter it is advisable to use not less'thanabout one mol of urea for each 3 mol of acid. Preferably, about 2 mole of urea are used with each mol of acid; Inasmuch as the urea seems to act as a flux as well as a reagent for the reaction, large excesses of urea may be employed. However, from an. economical point of view, a ratio of about 3 mols of urea to each mol of acidrepresents the normal upper limit of urea consumption. It should be noted that urea is inexpensive as compared with the pyridine monocarboxylic acids; furthermore, such by-products of the reaction as biuret and cyanuric are recoverable and salable. Thus it will be seen that the process of myinvention enjoys carboxylic acid that is utilized since its melting point and that of the corresponding amide will influence the fluidity of the reaction mass. Thus, for one example, when nicotinic acid is reacted with molten urea in accordance with my invention to produce nicotinamide which has a melting point of about 131 C., a reaction tempera ture of about 180 to about 220 C. is very satisfactory. Ingeneral, the temperature is so controlled that the reaction mass is kept in a fluid condition without reaching a stagewhere exces- I sive foaming occurs.

The amidization, according to this invention, is carried out in the presence of a catalyst consisting of or containing the element boron. While common boron compounds such as borax and sodium perborate are suitable catalysts, the pr ferred catalyst is boric acid. In my copending application, Serial No. 470,817, now Patent 2,419,831, April i, 1947, I have disclosed that other suitable amidization catalysts consist of or contain elements of Groups V and VI of the Mendeleif Periodic System having an atomic number between 15 and 92, inclusive. Representative catalysts are diammonium phosphate, bismuth sulfate, ammonium vanadate, arsenious oxide and selenium molybdate. Two or more catalysts may be used or the catalyst may be a compound of two or more active elements, e. g., ammonium borotungstate or phosphomolybdate; Preferred catalysts are boric acid andammonium molybdate. Of course, the catalysts vary in their activity but the catalytic amount used will generally be in the range of about 0.1 to about 5.0% of the weight of the entire reaction mass.

In some instances, in conducting the amidization it may be helpful to add a fluidizing medium (a high boiling point liquid) such as naphthalene, kerosene, quinoline, nitrobenzene or chloronaphthalene. ,v

As an illustrative example of the process of my invention, there may be cited the production of nicotinamide. :To 120 parts by weight of urea are added 123 parts of nicotinic acid mixed with 0.3 part of boric acid. The entire mixture is heated and brought to a temperature of about 180 to 220 C. In less thanJ3O minutes the reaction may be considered completed. It is desirable to agitate the reaction mass while-the reaction is -in progress. The pure nicotinamide product may be recovered from the'reaction mass by known methods, e. g., crystallization from suitable solvents.

Some'ammonia may be evolved in the course of the reaction and, accordingly, in some instances it may be advisable to carry out the operation in a closed system under pressure.

Instead of the free pyridine monocarboxylic acids, the corresponding ammonium salts may be converted to amides by heating them in the presence of urea and a boron catalyst of the present invention. When the ammonium salts or mixtures of the ammonium salts and the free acids are utilized in the amidization process, appreciably less urea is required than when free acids alone are used.

In view of the foregoing description, it will be understood that the reaction temperature and time will vary considerably with the particular material, free acid or ammonium salt, that is to be converted, with the selected proportion of urea and with the chosen catalyst.

Obviously, many modifications of the basic process of my invention Willsuggest themselves to those skilled in the art. For example, the operation may be made continuous by suspending the comminuted'pyridine monocarboxylic acid in molten urea containing catalyst and by pumping the fluid mixture through a heated tube maintained at reaction temperature; the heated tubular reactor is of sufficient length to discharge a mass in which the, original acid has reached a satisfactory stage of conversion to the amide.

The term, pyridine monocarboxylic acids, as used in this specification and the appended claims, comprehends benzopyridine monocarboxylic acids, such as quinaldinic acid.

The above description and examples are intended to be illustrative only. Variations of my invention conforming to its spirit are to be considered Within the scope of the claims.

What I claim is:

1. The process for the amidization of pyridine monocarboxylic acid compounds of the class consisting of pyridine monocarboxylic acids and their ammonium salts, which comprises reacting a said compound with urea in the proportions of about 2 mols of urea for each mol of said compound in the'presence of a boron catalyst, and recovering thus produced amide from the resulting reaction mass.

2. The process for the amidization of pyridine monocarboxylic acid compounds of the class consisting of pyridine monocarboxylic acids and their ammonium salts, which comprises reacting a said compound with urea at a temperature in the range of about to about 280 C. in the presence of a boron catalyst, and recovering thus produced amide from the resulting reaction mass.

3; The process for the amidization of pyridine monoca rboxylic acid compounds of the class consisting ofpyridine monocarboxylic acids and their ammonium salts, which comprises reacting a said compound with urea in the proportions of about 2 mols of urea for each moi of said compound at a temperature in the range of about 150 to about 280 C. in the presence of both a boron catalyst and a catalyst containing 'an element selected from Groups V and VI of the-Mendelefi Periodic System and having an atomic number between 15 and 92 inclusive, and recovering thus produced amide from the resultive reaction mass.

--4. The process iorthe amidization of pyridine inonocarboxylic acid compounds of the class consisting of pyridine monocarboxylic acids and their ammonium salts, which comprises reacting a said compound with urea at a temperature in the range of about 150 to about 280 C. in the presence of both boric acid and ammonium molybdate as catalysts, and recoverin thus produced amide from the resulting reaction mass.

5. The process for the production of nicotinamide, which comprises reacting a nicotinic acid compound of the class consistin of nicotinic acid and its ammonium salt with urea in the proportions of about 2 mols of urea for each mol of said compound in the presence of a boron catalyst and recovering thus produced nicotinamide from the resulting reaction mass.

6. The process for the production of nicotinamide, which comprises reacting a nicotinic acid compound of the class consisting of nicotinic acid and its ammonium salt with urea in the presence of a boron catalyst, maintaining the reaction at a temperature in the range of about 150 to about 280 C., and recovering thus produced nicotinamide from the resulting reaction mass.

'7. The process for the production of nicotinamide, which comprises reactin a nicotinic acid compound of the class consisting of nicotinic acid and its ammonium salt with urea in the proportions of about 2 mols of urea for each mol of said compound in the presence of both a boron catalyst and a molybdenum catalyst, maintaining the reaction at a temperature in the range of about 150 to about 280 C., and recovering thus produced nicotinamide from the resulting reaction mass. 7

8. The process for the production of nicotinamide, which comprises reacting a nicotinic acid compound of the class consisting of nicotinic acid and its ammonium salt with urea in the presence of boric acid as catalyst, maintaining the reaction at a temperature in the range of about to about 230 C., and recovering thus produced nicotinamide from the resulting reaction mass.

9. The process for the production of nicotinamide, which comprises reacting a nicotinic acid compound of the class consisting of nicotinic acid and its ammonium salt with urea in the presence of both boric acid and ammonium molybdate as catalysts, maintaining the reaction at a temperature in the range of about 170? to about 230 C., and recovering thus produced nicotinamide from the resulting reaction mass.

10, The process for the production of nicotinamide, which comprises reacting nicotinic acid with urea in the proportions of about 2 mols of urea for each mol of nicotinic acid in the presence of boric acid as catalyst, maintaining the reaction at a temperature in the range of about 170 to about 230 C., and recoverin thus produced nicotinamide from the resulting reaction mass.

PAUL W. GARBO.

REFERENCES CITED The following references are of record in the file of this patent:

Garbo Apr. 29, 1947 

